The role of statins in BC prevention remains controversial. Based on data derived from studies involving BC cells, statins may have anti-invasive and antiangiogenic effects, and they may induce apoptosis through 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition. These beneficial effects of statins may be due to the lowering of serum lipoproteins or to a direct effect of statins through HMG-CoA reductase inhibition. However, prior studies did not account for changes in lipid levels secondary to statins and the impact that this may have on BC risk.

To help clarify the place that statins have in BC carcinogenesis, researchers conducted a retrospective, population-based cohort study using data from Finnish national registries to investigate the association between serum cholesterol, statin use, and BC mortality.

The Finnish Cancer Registry houses data on 99% of cancer cases in Finland. Mammography screening—which is offered every 2 years for women aged 50 to 69 years—has an 82% compliance rate. This study included registry data on all females who were newly diagnosed with invasive BC between January 1, 1995, and December 31, 2013, who had hormone receptor data available and at least one cholesterol measurement recorded. While information on tumor grade was unavailable, tumor histological characteristics were available for 99.9% of cases. Diagnostic and procedural codes were obtained from both inpatient and outpatient visits. A Charleston Comorbidity Index was calculated based on data from the Care Register for Health Care database.

Lipid profile data were gathered from Finnish hospital districts and were categorized by target levels of 193.05 mg/dL for total cholesterol, 46.33 mg/dL for HDL, 115.83 mg/dL for LDL, and 150.44 mg/dL for triglycerides.

The investigators evaluated the changes in cholesterol following the initiation of statin therapy beginning after the first year of treatment. Patients were stratified based on changes in this lipid parameter (i.e., no change, decrease, increase in mean total cholesterol). Data from the Social Insurance Institute, which houses the national prescription database, served as the source of information on statin use. A yearly total milligram amount for each statin was calculated, and cumulative use between different statins was standardized based on the defined daily dose (DDD) as defined by the World Health Organization. The yearly dosage of statins was calculated using an intensity variable that considered the cumulative yearly DDD amount and the cumulative duration of use.

The primary focus of this study was to compare the risk of BC death between statin users and nonusers and to determine if there was any correlation with statin use. The secondary analysis looked for any correlation between patients’ lipid profile adjusted for statin use or cholesterol level and statin dose, any decrease in cholesterol levels, and hormone receptor status.

The study population consisted of 13,378 females with BC (median age: 62 years). During 4.5 years of follow-up, 16.4% of patients died, including 7% from their BC diagnosis. Among those with hypercholesterolemia, 31.2% had an elevated mean total cholesterol (>193.05 mg/dL) prior to their BC diagnosis, and over one-half (50.3%) had a high mean total cholesterol level following their BC diagnosis. Among the total population, 40.7% had been prescribed a statin.

Using multivariant analysis, researchers found that stain use before BC diagnosis was associated with a 41% increased risk of BC death compared to nonuse (hazard ratio [HR] = 1.41; 95% CI, 1.18-1.68; P <.001). This increased risk was not dose dependent. Even when adjusting for total cholesterol level, there was a 22% increased risk of BC death associated with statin use (HR 1.22; 95% CI, 1.02-1.46; P = .03). However, an opposite picture emerged when statins were prescribed following a BC diagnosis.

Postdiagnostic statin use had a significant inverse association with BC death following adjustment for lipid parameters (e.g., total cholesterol [HR 0.85; 95% CI, 0.73-1.00; P = .05] and LDL [HR = 0.84; 95% CI, 0.72-0.99]). The reduction in BC death increased in correlation with increasing intensity of statin use (i.e., as the tertile increased [e.g., LDL tertiles after BC diagnosis: first, 100.39 mg/dL or less; second, higher than 100.39 to 128.69 mg/dL; and third, >128.69 mg/dL] the HR decreased [HR = 1.04; 0.73, 0.66, respectively], with the latter two being statistically significant).

About 80% of study participants experienced a decrease in their median cholesterol level. When risk of BC death was stratified based on change in cholesterol level following the start of statin therapy, postdiagnostic statin use was associated with a 51% significantly reduced risk of BC death when the mean total cholesterol decreased subsequently (HR = 0.49, 95% CI; 0.32-0.75; P = .001). Increases or no changes in total cholesterol levels did not affect BC deaths. However, the possible beneficial effects of statins on BC risk did not persist long term as there was no association between BC death and postdiagnostic statin use in lag-time analyses at 1, 3, and 5 years. The reduction in BC death was only seen in patients with estrogen receptor–positive tumors (HR = 0.82; 95% CI, 0.68-0.99; P = .03) but not in other BC subtypes (e.g., triple-negative or human epidermal growth factor receptor 2 BC). Overall, there was a 20% reduction in overall mortality among statin users versus nonusers when adjusted for serum cholesterol level (HR = 0.80; 95% CI, 0.72-0.88; P <.001)

Patients who have had BC are at increased risk of cardiovascular disease and may be prescribed lipid-lowering therapy. Pharmacists should be aware of the possible beneficial effect of statin therapy among their female BC patients.

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